The Albumin in Subarachnoid Hemorrhage (ALISAH) Multicenter Pilot Clinical Trial

Abstract

Background and Purpose Human albumin has been shown to exert neuroprotective effects in animal models of cerebral ischemia and humans with various intracranial pathologies. We investigated the safety and tolerability of 25% human albumin (ALB) in patients with subarachnoid hemorrhage (SAH). Methods The ALISAH (Albumin in Subarachnoid Hemorrhage) Pilot Clinical Trial was an open-label, dose-escalation study. We intended to study 4 different dosages of ALB of increasing magnitude (0.625 g/kg: tier 1; 1.25 g/kg: tier 2; 1.875 g/kg: tier 3; and 2.5 g/kg: tier 4). Each dosage was to be given to 20 adult patients. Treatment was administered daily for 7 days. We investigated the maximum tolerated dose of ALB based on the rate of severe-to-life-threatening heart failure and anaphylactic reaction, and functional outcome at 3 months. Results We treated 47 adult subjects: 20 in tier 1; 20 in tier 2; and 7 in tier 3. We found that doses ranging up to 1.25 g/kg/day × 7 days were tolerated by patients without major dose-limiting complications. We also found that outcomes trended towards better responses in those subjects enrolled in tier 2 compared to tier 1 (OR: 3.0513; CI: 0.6586 – 14.1367) and to the International Intra-operative Hypothermia for Aneurysm Surgery Trial cohort (OR: 3.1462; CI: 0.9158 – 10.8089). Conclusions ALB in doses ranging up to 1.25 g/Kg/day × 7 days was tolerated by patients with SAH without major complications and may be neuroprotective. Based on these results, planning of the ALISAH II, a Phase III, randomized, placebo-controlled trial to test the efficacy of ALB is underway. Clinical Trial Registration Information: NCT00283400 (clinicaltrials.gov) http://clinicaltrials.gov/ct2/show/NCT00283400?term=subarachnoid+hemorrhage+houston&rank=1

Multicenter Prospective Cohort Study on Volume Management After Subarachnoid Hemorrhage

“…Primarily, cerebral perfusion pressure should be maintained by intracranial pressure control, and then systemic blood pressure is lowered to decrease peripheral vascular resistance; inotropic action is increased using dobutamine and other agents; and preload such as volume expansion is increased, for example, by loading the appropriate amount of albumin. 30 In this study, the incidence of DCI did not differ significantly between the good grade and poor grade groups, but the incidence of symptomatic cerebral vasospasm was significantly lower in the poor grade group (Table 1). This was because many patients in the poor grade group could not be neurologically evaluated because of impaired consciousness.…”

Delayed neurological deterioration after subarachnoid haemorrhage

“…115 In an openlabel doseescalation trial of intravenous human albumin, patients with SAH tolerated up to 1.25 g/kg per day of albumin and, at this dose, showed a trend towards improved outcome. 116 Erythropoietin was neuroprotective in animal models of ischaemic stroke, prevented loss of autoregulation after SAH in rats, 117 and reduced angiographic vaso spasm and delayed neurological deterioration, and improved outcome after SAH in rabbits. 118 The com pound inhibits apoptosis and stimulates neuro genesis and angio genesis.…”

Human Albumin Improves Long-Term Behavioral Sequelae After Subarachnoid Hemorrhage Through Neurovascular Remodeling

“…Indeed, administration of albumin has been associated with improved outcomes in SAH beagle dogs (9) and in patients (10). More recently, the Albumin in Subarachnoid Hemorrhage (ALISAH) pilot study revealed that 1.25 g/kg/d albumin treatment is safe in patients with SAH and may produce a better outcome (11). However, the full-scale preclinical characteristics of albumin in SAH and its potential mechanisms have not been defined.…”